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Steel Syndrome (MIM #615155) was first described by Steel et al. in 1993 as an orthopedic syndrome observed in 23 Hispanic children from Puerto Rico (Steel et al., J. Bone Joint Surg. Am. 75: 259-264, 1993). The main clinical features include congenital bilateral hip and radial head dislocation, short stature, carpal coalitions, scoliosis, foot abnormalities, and mildly dysmorphic features.
Clinical and genetic evaluation of patients with STLS pointed to a distinct genetic syndrome different from other well-characterized skeletal dysplasias and connective tissue disorders. Attempts at identifying a common molecular etiology for the characteristic features of STLS were unsuccessful until 2015 when Gonzaga-Jauregui et al. reported that the COL27A1 p.Gly697Arg variant, when in homozygosity, is a molecular cause of Steel Syndrome and suggested that this missense change is a founder variant in individuals of Puerto Rican descent (Gonzaga-Jauregui et al., Europ. J. Hum. Genet. 23: 342-346, 2015), Subsequent studies in large cohorts including multi-ethnic populations have identified the p.Gly697Arg variant in additional individuals. Additional cases have been published linking novel rare recessive mutations in COL27A1 with osteochondrodysplastic phenotypes manifesting features overlapping those of the reported Puerto Rican patients with Steel Syndrome, but also with additional features not attributed to Steel Syndrome, such as hearing loss and speech delay (Gariballa et al., Am J Med Genet A. 2017; 173(5):1257-1263; Kotabagi et al., Clin Genet. 2017; 92(3):323-326).